Structural basis for different specificities of acyltransferases associated with the human cytosolic and mitochondrial fatty acid synthases
| Autor: | Stephanie Misquitta, Kathryn L. Kavanagh, Grazyna Kochan, Gabor Bunkoczi, Stuart Smith, Alexandra Rojkova, Xiaoqiu Wu, Wen Hwa Lee, Udo Oppermann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Clinical Biochemistry
Mitochondrion Crystallography X-Ray 01 natural sciences Biochemistry Substrate Specificity chemistry.chemical_compound Cytosol Catalytic Domain Drug Discovery Fatty Acid Synthase Type II Transferase genetics Peptide sequence chemistry.chemical_classification 0303 health sciences Fatty Acids General Medicine Mitochondria Fatty Acid Synthase Type I Fatty Acid Synthetase Complex Type I Molecular Medicine Stereochemistry enzymology Molecular Sequence Data Biology 010402 general chemistry chemistry Article 03 medical and health sciences Fatty Acid Synthetase Complex Type II Biosynthesis Humans Computer Simulation Amino Acid Sequence Molecular Biology 030304 developmental biology Pharmacology Sequence Homology Amino Acid Metabolism 0104 chemical sciences Enzyme CHEMBIO Acyltransferases Mutagenesis Site-Directed Mutant Proteins biosynthesis Sequence Alignment metabolism |
| Zdroj: | Chemistry and biology. (6) |
| ISSN: | 1879-1301 |
| Popis: | SummaryAnimals employ two systems for the de novo biosynthesis of fatty acids: a megasynthase complex in the cytosol (type I) that produces mainly palmitate, and an ensemble of freestanding enzymes in the mitochondria (type II) that produces mainly octanoyl moieties. The acyltransferases responsible for initiation of fatty acid biosynthesis in the two compartments are distinguished by their different substrate specificities: the type I enzyme transfers both the acetyl primer and the malonyl chain extender, whereas the type II enzyme is responsible for translocation of only the malonyl substrate. Crystal structures for the type I and II enzymes, supported by in silico substrate docking studies and mutagenesis experiments that alter their respective specificities, reveal that, although the two enzymes adopt a similar overall fold, subtle differences at their catalytic centers account for their different specificities. |
| Databáze: | OpenAIRE |
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